Preparation of benzonitriles

ABSTRACT

A method of preparing a benzonitrile of the formula   WHEREIN R1 is a substituent nitro group and R2 is a substituent halogen atom, which comprises reacting an R1, R2-benzoyl chloride with an alkanesulphonyltrichlorophosphazene at a temperature of between 150* C. and 190* C. The benzonitrile products are useful as intermediates in the preparation of amidino ureas having antimalarial activity.

22 Filed:

United States Patent [1 1 Grivsky PREPARATION OF BENZONITRILES [75]Inventor: Eugene M. Grivsky, Chapel Hill,

[73] Assignee: Burroughs Wellcome Co., a Corp. of

North Carolina and Wellcome Foundation Ltd., London, England May 28,1971 [21] Appl. No.: 148,172

[30] Foreign Application Priority Data May 29, 1970 Great Britain25,984/70 [52] U.S. Cl. 260/465 B, 260/465 E, 260/465 G [51] Int. Cl.C07c 121/02, C070 121/52 [58] Field of Search 26.0/999; 260/465 B,

[5 6] References Cited OTHER PUBLICATIONS Homing: Organic Syntheses,Col. Vol. III, pp. 646-648, John Wiley & Sons, Inc. (1955) Migrdichian:The Chemistry of Organic Cyanogen [111 3,742,014 June 26, 1973Compounds, Reinhold Publ. Corp., p. 29 (1947).

Primary Examiner-Lewis Gotts Assistant Examiner-Dolph H. TorrenceAttorney-Sewall P. Bronstein, John D. Woodberry, Robert T. Gammons,Donald Brown, Robert L. Goldberg and Robert F. OConnell [57] ABSTRACT Amethod of preparing a benzonitrile of the formula 37 Claims, No DrawingsPREPARATION OF BENZONITRILES This invention relates to the preparationof benzonitriles.

Methods for preparing benzonitriles are well-known in the art, thecorresponding benzoic acids commonly being used as starting materials.One such method involves conversion of the acid to its chloride andthence to its amide followed by dehydration of the latter by reactionwith thionyl chloride in benzene or toluene, as represented by thefollowing reaction scheme (I) SOCl Ar-CONH; Ar-CN 80-100 (I) Analternative preparation (see, for example, Org. Synth., Col. Vol. III,646) is to heat the acid with one equivalent of an arylsulphonamide andtwo equivalents of phosphorus pentachloride. p-Toluenesulphonamide iscommonly used, the reaction being represented by the scheme (II) Both ofthe above methods possss disadvantages when the deisred benzonitrileproduct is of formula (III) tially heated together the reaction isexothermic and difficult to control, although some degree of moderationmay be affected by conducting the reaction under an inert atmospheresuch as nitrogen.

The benzonitriles of formula (III) are valuable among other things asintermediates for producing by reduction the corresponding anilines offormula X, the substituent nitro group R being converted to an aminogroup by the use of a reducing agent such as, for example, stannouschloride in the presence of hydrochloric acid, or iron and acetic acidas shown in the following reaction scheme R IIZN m4: (u) @AJMX) 1 2 R(III) Preferred compounds of formula (III) are those wherein thesubstituent halogen atom is chlorine, bromine, fluroine or iodine; themost preferred compounds are those wherein the halogen is chlorine.

The anilines referred to above are useful for conversion to1-amidino-3-phenyl ureas XI such as those described in U.S. applicationSer. No. 650,225, filed June NC N II NH H+ in H2O (mg. H01 in water) Thecompoundsof formula XI as well as the pharmaceutically acceptable acidaddition salts thereof are all useful as antimalarials. In particularthe compounds of formula XI are active against P.Gallinaceum in chicksand P. Vinckei and P. Berghei in mice.

For the treatment or prophylaxis of malaria the compounds may bepresented in tablet form or as an injectable solution. In treatinginfections in animals and mammals (e.g., man), a dose of from 1 to 100mg/kg of bodyweight would be used.

It has now been found that, for the preparation of benzonitriles offormula (III) by method (II), when the arysulphonamide is replaced by alower alkanesulphonamide, for example, methanesulphonamide,ethanesulphonamide, propylsulphonamide, butylsulphonamide (e.g.,n-butylsulphonamide) etc, several important advantages are obtained:

a. The reaction proceeds more smoothly and requires a lower finaltemperature l-l80 C as compared with 2l0230C.

b. The method is more generally applicable and the yields areconsistently good, percent or more of the theoretical value.

c. Isolation and purification of the product are much simplified as onlythe nitrile product is insoluble in water.

The process of the present invention may be carried out in the samemanner as previously described for the preparation of nitriles usingp-toluenesulphonamide. except for the final thermal conditions. When thealkanesulphonamide used is methanesulphonamide the overall reaction ofthe present invention may be represented by the scheme (IV) Ar'COOI-I CHSO NH 2PC1 3I-ICl 2POCI3 CI'IaSOzCI ArCN (IV) As preferably carried out,the reactants shown in scheme (IV) are present in the ratio of one moleof the benzoic acid, one mole of methanesulphonamide and two moles ofphosphorus pentachloride, as shown. The

reactants are mixed together in a reaction vessel having distillationmeans and warmed cautiously to a temperature not exceeding C whilstthree moles of hydrogen chloride are evolved. The temperature of thereaction mixture may then be raised gradually to the final level ofaround 180 C whilst two moles of phosphorus oxychloride distill off andthe reaction is completed with formation of the nitrile.

Formation of the nitrile is believed to begin at a temperature of about150 C, and proceeds at a convenient rate at 180.

According to the present invention in one aspect therefore there isprovided a method of preparing a benzonitrile of the formula (III) whichcomprises reacting the corresponding benzoic acid with a loweralkanesulphonamide (preferably one to four carbons) and phosphoruspentachloride, at a temperature of preferably not less than about 150 Cand not more than 190 C. and most preferably between 175 C to 180 C.

Examination of the successive formation of intermediates and by-productsduring the course of the reac-' tion shown by scheme (IV) suggests thatthe reaction proceeds as follows:

a. when the temperature of the reaction mixture is below 90 C.,

i. The benzoic acid reacts with one mole of phosphorus pentachloride togive the benzoyl chloride and one mole each of phosphorus oxychlorideand hydrogen chloride:

ALCOOH PCl HCl POCl Ar'COCI The methanesulphonamide reacts with thesecond mole of phosphorus pentachloride to givemethanesulphonyltrichlorophosphazene and the other two moles of hydrogenchloride:

The methanesulphonyltrichlorophosphazene is an identifiable solid whichb. reacts with the benzoyl chloride from (V) at a tem perature greaterthan about 150 C. to yield the henzonitrile by elimination ofmethanesulphonyl chloride and the second mole of phosphorusoxy'chloride:

ArLCOCl CH SO NPCL, POCl CH SO Cl Ar.CN.

(Vll) It will be appreciated from the foregoing; that the benzonic acidused as starting material in (IV) may be replaced by the benzoylchloride, when only one mole of phosphorus pentachloride is required andthe reaction follows the scheme:

Ar COCl CH SO NH PCl (V111) POCl ZHCl cn so ci ArCN It will also beappreciated, from (Vlil), that the benzonitrile may be prepared by thedirect reaction between the benzoyl chloride andmethanesulphonyltrichlorophosphazene.

Thus inanother aspect the present invention provides a method ofpreparing a benzonitrile of the formula (111) which comprises reactingthe corresponding benzoyl chloride with an alkanesulphonamide and 4phosphorus pentachloride, at a temperature of not less than about C andnot more than 190 C.

in yet another aspect the present invention provides a method ofpreparing a benzonitrile of the formula (III) which comprises reactingthe corresponding benzoyl chloride with analkanesulphonyltrichlorophosphazene at a temperature of preferably notless than about 150 C and not more than 190 C, and most preferably C toC wherein the benzoyl chloride is optionally prepared in situ byreacting the corresponding benzoic acid with phosphorus pentachloride,and wherein the alkanesulphonyltrichlorophosphazene is optionallyprepared in Situ by reacting the corresponding alkanesulphonamide withphosphorus pentachloride.

ln another aspect the present invention provides the benzonitriles offormula ([11) when prepared by any of the methods provided hereinbefore.

The final products of the process of the invention, as exemplified byscheme (IV), are hydrogen chloride, phosphorus oxychloride,methanesulphonyl chloride and the benzonitrile, of which the former twoare eliminated from the reaction mixture by distillation. Excessphosphorus pentachloride and the methanesulphonyl chloride may beremoved by treating the mixture with a cold, preferably aqueous organicor inorganic base. Dilute ammonium hydroxide and dilute aqueoussolutions of alkali metal hydroxides or carbonates are suitable, butdilute ammonium hydroxide is preferred since the methanesulphonamidestarting material is produced by the reaction and may be recovered ifdesired. The benzonitrile product from (IV) is preferably collected byfiltration and is essentially pure at this point but may berecrystallised from appropriate solvents if desired, or purified bysublimation.

Table l at the end of the following Examples shows the results of twoseries of experiments wherein a variety of benzoic acids were convertedto the corresponding benzonitriles, p-toluenesulphonamide being used inthe one series and methanesulphonamide in the other. The latter seriesin all instances involving the method of the present invention as givenin Examples l-4 gave the better results in all cases.

The invention will now be described with reference to the folloiwngExamples. All temperatures are in degrees Celsius.

EXAMPLE 1 Methanesulphonamide (9.5 g., 0.1 moie) and phosphoruspentachloride (21.0 g., 0.1 mole) were gently heated together undernitrogen and the mixture maintained at a temperature of 60 C. for 1hour. Evolution of hydrogen chloride began at 40 C; the gas evolved wastrapped and titrated, the theoretical amount (two equivalents) beingrecorded. The reaction mixture was then heated at 90 C. for 10 minuteswhen a white iiquid formed which on cooling gave white hygroscopiccrystals of methanesulphonyltrichlorophosphazene, Cl-i S0 N:PCl inalmost quantitative yield. This compound was recrystallised from a 1:8benzene-hexane mixture, m.p.5556 C. in a sealed melting-point tube.(Maximum precautions should be taken when manipulating this compound asit is markedly vesicant and caused painful end severe skin reactions).

Analysis Calculated for CH SO N:PCl C=5.2l; H=l.3l; N=6.l

Found C=5.40; H=1.50; N=6.3

To the crude phosphazene was added over a period of minutes and under anitrogen atmosphere (flow) a total of 22.0 g. (0.1 mole) of3-chloro-2-nitroben2oyl chloride, obtained from the reaction of3-chloro-2- nitrobenzoic acid with thionyl chloride and recrystallised(m.p. 61 C.) from a 1:8 benzene-pentane mixture (Analysis CalculatedC=38.21; H=1.37; N=6.36. Found C=38.29; l-l=l.l7; N=5.93). With theaddition completed the temperature of the mixture was slowly raised to150 C. to initiate the pyrolytic reaction and maintained at this levelfor 10 to minutes. Finally the temperature was progressively raised toaround 180 C. when the theoretical quantity, one equivalent, ofphosphorus oxychloride distilled over during minutes. The reactionmixture was then cooled and treated with crushed ice and dilute ammoniumhydroxide; the solid, crude product was filtered off and purified bysublimation under reduced pressure to give 16.2 g. of3-chloro-2-nitrobenzonitrile. m.p. 85 C., 88 percent yield. 7

Analysis Calculated for C-,l-l ClN O C=46.03; H=l.64; Cl=l9.45; N=l5.35.

Found C=46.32; H=l.90; Cl=19.60;N=15.10.

EXAMPLE 2 3-Chloro-5-nitrobenzoic acid (20.1g., 0.1M),methanesulphonamide (9.5g., 0.1M) and phosphorus pentachloride (42g.,0.2M) were stirred together under nitrogen. An initial exothermicreaction took place during which the temperature of the mixture rose to5060C., three equivalents of hydrogen chloride were evolved and thereaction mixture became liquid. The temperature of the reaction mixturewas then slowly raised to 180 C and maintained near this for 30 minutesuntil no more phosphorus oxychloride distilled over, 0.1M of this latterbeing recovered at l45l 50C and a second 0.1M at l75l82C. At the end ofthis distillation period some methanesulphonyl chloride distilled overalso. The reaction mixture was then cooled and cold dilute ammoniumhydroxide added. The solid, crude product was filtered off andrecrystallised from a benzenehexane mixture to give pure 3-chloro-5-nitrobenzonitrile, m.p. 93 C., in 90 percent yield.

EXAMPLE 3 2-Chloro-3-nitrobenzoic acid (20.2g.,0.1M),methanesulphonamide (9.5g., 0.1M) and phosphorus pentachloride(42g, 0.2M) were gently heated together under nitrogen, evolution ofhydrogen chloride occurring over the temperature range 10-60C. When thisevolution had subsided and the reaction mixture had become liquid, dueto the formation of phosphorus oxychloride, the temperature of themixture was slowly raised to 160 C and maintained at this for 20 minutesuntil no more phosphorus oxychloride distilled over. The mixture wasthen heated to 185 C and this temperature maintained for 30 minuteswhilst more phosphorus oxychloride distilled. The cooled reactionmixture was then treated with crushed ice and dilute ammonium hydroxideand the solid, crude 2-chloro-3- nitrobenzonitrile thus obtainedfiltered off, washed with water, dried and recrystallised from aqueousetha- 1101 to. give 16.5g. of purified product, m.p. 104, yield percent.

EXAMPLE 4 A mixture of 2-bromo-4-nitrobenzoic acid (12.1g, 0.05M),methanesulphonamide (4.8g, 0.05M) and phosphorus pentachloride (21g,0.1M) was gently heated under nitrogen; hydrogen chloride was evolvedover the temperature range 5060 C and the reaction mixture becameliquid. The temperature of the mixture was slowly raised to 185 C andmaintained at this for 30 minutes until no more phosphorus oxychloridedistilled over, 0.05M of this'latter being recovered when thetemperature was l50 -l55 C and a further 0.05M at a temperature ofl75l82C. The reaction mixture was then cooled and treated with ice anddilute ammovnium hydroxide and the nitrile isolated as before. 2

-Bromo-4-nitrobenzonitrile, m.p. 126 C., was obtained in 91 percentyield.

EXAMPLE 5 Preparation of 4-amino-2-chlorobenzonitrile To a solution ofstannous chloride (SnCli 2H O) (40 g., 0.17M) in concentratedhydrochloric acid (25 ml. of 37 percent) at 20 C, portions of2-chloro-4- nitrobenzonitrile (6.1 g., 0.034M in total) are added over20 minutes, with stirring and external cooling when necessary to keepthe temperature below 30 C. After all the reactant has been added, thereaction mixture (a yellow slurry) is stirred for 2-3 hours and thensome excess hydrochloric acid added, followed by 40 percent caustic sodasolution until an alkaline pH is obtained. It is necessary to stirmechanically and cool during this operation to keep the temperature atabout 25 After standing for about 30 minutes the crude product isfiltered off and washed with water until free from alkali. It is thenrecrystallised from an ether/hexane mixture to give 4.8 g. (96 percentyield) of 4-amino-2- chloro-benzonitrile m.p. 108-1 10 C. This may befurther recrystallised from water.

Example 6 Preparation of 2-chloro-5-aminobenzonitrile A mixture of2-chloro-5-nitrobenzonitrile (9.1 g., 0.05 mole) in 124 ml. of glacialacetic acid and anhydrous stannous chloride, SnCl (40.0 g., ca. 0.2mole), was heated to l00C with stirring and dry hydrogen chloride waspassed into the reaction mixture until it was saturated (45-60 minutes).After standing for 8 hours the tin complex thus formed was filtered off,washed with glacial acetic acid and decomposed by means of 50 ml. of 40percent sodium hydroxide solu tion at 10-15C in the usual manner. Theresultant amine was filtered off, washed with water and dissolved inanhydrous ether. The ether extracts were evaporated by dryness in vacuoto give 6.3 g. of 2-chloro-5- aminobenzonitrile (yellow needles), mp.133 C (yield 83 percent). This product may be further purified bysublimation in vacuo to give white crystals, m.p. l356.

Example 7 4-Chloro-3-cyanoaniline (6.1 g. dicyandiamide (3.7 g. water 16ml.) and concentrated hydrochloric acid (3.6 ml.) were heated underreflux for 30 minutes. With cooling a hydrochloride crystallised whichwas collected by filtration and washed with a little water. This crudesalt was dried and recrystallised from alcohol.4-Chloro-3-cyanophenyl-biguanide hydrochloride then separated as whiteneedles (6.4 g.)., m.p. 233 with effervescence. The base was obtained assmall white needles when the solution of this salt was made alkalinewith sodium hydroxide; recrystallised from alcohol, it formed colourlessprisms, m.p. 202 with effervescence.

The biguanide base (3.2 g.) was dissolved in N- ethanesulphonic acid (32ml.) and kept at 90 for 2 hours, during which period colourless crystalsof 1- amidino-3-(4-chloro-3-cyanophenyl) urea ethanesulphonateseparated. This salt was collected after cooling (2.8 g.), and wasrecrystallised from methanol (or water) and formed white needles, m.p.219. The base was obtained by treating an aqueous solution of the saltwith sodium hydroxide. lt formed white needles, m.p. 222, which could befurther purified by recrystallisation from alcohol. This substance wassparingly soluble in water.

Example 8 By the method of the previous example, 3-chloro-4-cyanoaniline was converted to 3-chloro-4- cyanophenylbiguanidehydrochloride, which formed white matted needles from methanol, m.p. 256with effervescence (the corresponding base formed white prisms fromalcohol, m.p. 184).

The biguanide g.) was dissolved in 0.5N- ethanesulphonic acid (100 ml.)and the solution was kept at 90 for 2 hours. With cooling, a high yieldof lamidino-3-(3-chloro-4-cyanophenyl) urea ethanesulphonatecrystallised in white prisms, m.p. 222 (the corresponding basecrystallised from alcohol had a m.p. 21 l).

What we claim is: l. A method of preparing a benzonitrile of the formulal wherein R is a substituent nitro group and R is a substituent halogenatom which comprises heating a mixture of an R, R benzoyl chloride ofthe formula II R (II) wherein R and R have the same meanings ashereinbefore with at least an equimolar amount ofalkanesulphonyltrichlorophosphazene of the formula III (lll) wherein Alkis an alkyl group having one to four carbon atoms at a temperature ofbetween C and 190 C.

2. A method according to claim 1 wherein the mixture is heated to atemperature of between l75 C. and C.

3. A method according to claim 1 wherein thealkanesulphonyltrichlorophosphazene ismethanesulphonyltrichlorophosphazene. v

4. The method of claim 3 in which R is nitro at the 3 position of thering and R is chloro at the 2 position of the ring.

5. The method of claim 3 in which R is nitro at the 4 position of thering and R is chloro at the 2 position of the ring.

6. The method of claim 3 in which R is nitro at the 5 position of thering and R is chloro at the 2 position of the ring.

7. The method of claim 3 in which R is nitro at the 6 position of thering and R is chloro at the 2 position of the ring.

8. The method of claim 3 in which R is nitro at the 2 position of thering and R is chloro at the 3 position of the ring.

9. The methodof claim 3 in which R is nitro at the 4 position of thering and R is chloro at the 3 position of the ring.

10. The method of claim 3 in which R is nitro at the 5 position of thering and R is chloro at the 3 position of the ring.

11. The method of claim 3 in which R is nitro at the 6 position of thering and R is chloro at the 3 position of the ring.

12. The method of claim 3 in which R is nitro at the 2 position of thering and R is chloro at the 4. position of the ring.

13. The method of claim 3 in which R is nitro at the 3 position of thering and R is chloro at the 4 position of the ring.

14. The method of claim 3 in which R is nitro at the 4 position of thering and R is fluoro at the 2 position of the ring.

15. The method of claim 3 in which R is nitro at the 5 position of thering and R is fluoro at the 2 position of the ring.

16. The method of claim 3 in which R is nitro at the 4 position of thering and R is bromo at the 2 position of the ring.

17. The method according to claim 1 wherein the substituent R is an atomof chlorine.

18. A method according to claim 1 wherein the R,R -benzoyl chloride is2-chloro-4nitro-benzoyl chloride.

19. A method according to claim 1 wherein the RJV-benzoyl chloride andthe alkanesulphonyltrichlorophosphazene are present in equimolaramounts.

20. A method according to claim 1 wherein an aqueous base is used toprecipitate the product benzonitrile.

21. A method according to claim 1 wherein ammonium hydroxide is used toprecipitate the product benzonitrile.

22. A method according to claim 1 wherein the R, R -benzoyl chloride isprepared in situ by reacting the R, R -benzoic acid of the formulawherein R and R have the meaning hereinbefore with at least an equimolaramount of phosphorus pentachloride.

23. A method according to claim 22 wherein the R,R -benzoic acid and thephosphorus pentachloride are present in equimolar amounts.

24. A method according to claim 22 wherein the R',R -benzoyl chloride isreacted with the alkanesulphonyltrichlorophosphazene at a temperature ofbetween 175' C. and 180 C.

25. A method according to claim 22 wherein thealkanesulphonyltrichlorophosphazene ismethanesulphonyltrichlorophosphazene.

26. A method according to claim 22 wherein the substituent R is an atomof chlorine.

27. A method according to claim 22 wherein the R,R -benzoyl chloride is2-chloro-4-nitrobenzoyl chloride.

28. A method according to claim 22 wherein an aqueous base is used toprecipitate the product benzonitrile.

29. A method according to claim 22 wherein ammonium hydroxide is used toprecipitate the product benzonitrile.

30. A method according to claim 1 wherein thealkanesulphonyltrichlorophosphazene is prepared in situ by reacting analkanesulphonamide of the formula alk. SO NH wherein Alk is as definedin claim 1 with at least an equimoler amount of phosphoruspentachloride.

31. A method according to claim 30 wherein the alkanesulphonamide andthe phosphorus pentachloride are present in equimolar maounts.

32. A method according to claim 30 wherein the R,R -benzoyl chloride isreacted with the alkanesulphonyltrichlorophosphazene at a temperature ofbetween 0. and C.

33. A method according to claim 30 wherein thealkanesulphonyltrichlorophosphazene ismethanesulphonyltrichlorophosphazene.

34. A method according to claim 30 wherein the substituent R is an atomof chlorine.

35. A method according to claim 30 wherein the R',R -benzoyl chloride is2-chloro-4-nitrobenzoyl chloride.

36. A method according to claim 30 wherein an aqueous base is used toprecipitate the product benzonitrile.

37. A method according to claim 30 wherein ammonium hydroxide is used toprecipitate the product ben-

2. A method according to claim 1 wherein the mixture is heated to atemperature of between 175* C. and 180* C.
 3. A method according toclaim 1 wherein the alkanesulphonyltrichlorophosphazene ismethanesulphonyltrichlorophosphazene.
 4. The method of claim 3 in whichR1 is nitro at the 3 position of the ring and R2 is chloro at the 2position of the ring.
 5. The method of claim 3 in which R1 is nitro atthe 4 position of the ring and R2 is chloro at the 2 position of thering.
 6. The method of claim 3 in which R1 is nitro at the 5 position ofthe ring and R2 is chloro at the 2 position of the ring.
 7. The methodof claim 3 in which R1 is nitro at the 6 position of the ring and R2 ischloro at the 2 position of the ring.
 8. The method of claim 3 in whichR1 is nitro at the 2 position of the ring and R2 is chloro at the 3position of the ring.
 9. The method of claim 3 in which R1 is nitro atthe 4 position of the ring and R2 is chloro at the 3 position of thering.
 10. The method of claim 3 in which R1 is nitro at the 5 positionof the ring and R2 is chloro at the 3 position of the ring.
 11. Themethod of claim 3 in which R1 is nitro at the 6 position of the ring andR2 is chloro at the 3 position of the ring.
 12. The method of claim 3 inwhich R1 is nitro at the 2 position of the ring and R2 is chloro at the4 position of the ring.
 13. The method of claim 3 in which R1 is nitroat the 3 position of the ring and R2 is chloro at the 4 position of thering.
 14. The method of claim 3 in which R1 is nitro at the 4 positionof the ring and R2 is fluoro at the 2 position of the ring.
 15. Themethod of claim 3 in which R1 is nitro at the 5 position of the ring andR2 is fluoro at the 2 position of the ring.
 16. The method of claim 3 inwhich R1 is nitro at the 4 position of the ring and R2 is bromo at the 2position of the ring.
 17. The method according to claim 1 wherein thesubstituent R2 is an atom of chlorine.
 18. A method according to claim 1wherein the R1,R2-benzoyl chloride is 2-chloro-4-nitro-benzoyl chloride.19. A method according to claim 1 wherein the R1,R2-benzoyl chloride andthe alkanesulphonyltrichlorophosphazene are present in equimolaramounts.
 20. A method according to claim 1 wherein an aqueous base isused to precipitate the product benzonitrile.
 21. A method according toclaim 1 wherein ammonium hydroxide is used to precipitate the productbenzonitrile.
 22. A method according to claim 1 wherein the R1,R2-benzoyl chloride is prepared in situ by reacting the R1, R2-benzoicacid of the formula
 23. A method according to claim 22 wherein theR1,R2-benzoic acid and the phosphorus pentachloride are present inequimolar amounts.
 24. A method according to claim 22 wherein theR1,R2-benzoyl chloride is reacted with thealkanesulphonyltrichlorophosphazene at a temperature of between 175* C.and 180* C.
 25. A method according to claim 22 wherein thealkanesulphonyltrichlorophosphazene ismethanesulphonyltrichlorophosphazene.
 26. A method according to claim 22wherein the substituent R2 is an atom of chlorine.
 27. A methodaccording to claim 22 wherein the R1,R2-benzoyl chloride is2-chloro-4-nitrobenzoyl chloride.
 28. A method according to claim 22wherein an aqueous base is used to precipitate the product benzonitrile.29. A method according to claim 22 wherein ammonium hydroxide is used toprecipitate the product benzonitrile.
 30. A method according to claim 1wherein the alkanesulphonyltrichlorophosphazene is prepared in situ byreacting an alkanesulphonamide of the formula alk. SO2NH2 wherein AlK isas defined in claim 1 with at least an equimoler amount of phosphoruspentachloride.
 31. A method according to claim 30 wherein thealkanesulphonamide and the phosphorus pentachloride are present inequimolar maounts.
 32. A method according to claim 30 wherein theR1,R2-benzoyl chloride is reacted with thealkanesulphonyltrichlorophosphazene at a temperature of between 175* O.and 180* C.
 33. A method according to claim 30 wherein thealkanesulphonyltrichlorophosphazene ismethanesulphonyltrichlorophosphazene.
 34. A method according to claim 30wherein the substituent R2 is an atom of chlorine.
 35. A methodaccording to claim 30 wherein the R1,R2-benzoyl chloride is2-chloro-4-nitrobenzoyl chloride.
 36. A method according to claim 30wherein an aqueous base is used to precipitate the product benzonitrile.37. A method according to claim 30 wherein ammonium hydroxide is used toprecipitate the product benzonitrile.